Chronic Lymphocytic Leukemia: Rapidly Changing Treatment Landscape

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in developed countries. CLL is diagnosed with absolute B lymphocyte count (B-ALC) >5000/micrL sustained for at least 3 months, morphologically mature-appearing small lymphocytes, and flow cytometry showing the typical immunophenotype of CLL cells. Different prognostic parameters are used to differentiate between low-and high-risk patients, which would affect treatment decisions. Rai and Binet staging systems are the two most commonly used in practice. There has been a significant change in how we manage patients in CLL over the last 5 years. We have shifted away from chemoimmunotherapy toward novel agents such as BTK, PIK3, and BCL-2 inhibitors, which are not only more efficacious but are also safer and better tolerated. New prognostic models are being developed, and it appears that minima residual disease (MRD) directed therapy will become the norm in the future. Many clinical trials are looking at various combinations of novel therapies, with a defined period of treatment based on MRD analysis, to enable patients to have a period of treatment-free remission instead of continuous therapy. In this chapter, we summarize the latest updates in CLL management

Ecoulement viscoplastique à chaud de métaux biphasés : modèles varationnels, influence de la répartition des phases et confrontations expérimentales.

The purpose of this thesis is the understanding and prediction of the behavior of polycrystals composed of two phases. The specificity of this problem is related to the microstructure of the material. This is both made ​​up of several crystallographic phases (allotropic) distinct (the material is in this sense a composite material) and crystals with a variety of shapes and orientations, which is conventional in the case of a polycrystalline material. With the idea that this double source of heterogeneity should affect the behavior at the macroscopic scale but also to smaller scales, we have addressed the problems encountered in forming the case of an austenitic-ferritic steel.L'objet de cette thèse est la compréhension et la prévision du comportement des polycristaux composés de deux phases. La spécificité de ce problème est liée à la microstructure du matériau. Celle-ci est à la fois constituée de plusieurs phases cristallographiques (allotropiques) distinctes (le matériau est en ce sens un matériau composite) et de cristaux présentant un grand nombre de formes et d'orientations, ce qui est classique dans le cas d'un matériau polycristallin. C'est avec l'idée que cette double source d'hétérogénéité doit avoir une influence sur le comportement, à l'échelle macroscopique mais aussi aux échelles plus fines, que nous avons abordé les problèmes de mise en forme rencontrés dans le cas d'un acier austéno-ferritique. L'enjeu de ce travail est de construire un modèle visant à reproduire les phénomènes observés lors de caractérisations expérimentales du matériau. L'hétérogénéité du matériau, la complexité de sa microstructure et l'aspect non déterministe attaché à sa description nous ont conduit à utiliser des modèles d'homogénéisation pour aborder ce problème. Le premier objectif fixé fut donc de faire la revue des caractéristiques du matériau d'étude et des méthodes d'homogénéisation existantes qui peuvent nous aider à le modéliser ; c'est l'objet des deux premiers chapitres de ce travail. A l'issue de cette synthèse bibliographique, nous nous interrogerons sur les spécificités de la description morphologique de ces polycristaux biphasés. L'absence de modèle permettant de caractériser l'influence de la répartition des phases sur le comportement mécanique d'un tel matériau nous conduira à proposer un nouveau modèle qui sera présenté au chapitre 3. Cette nouvelle description étant posée, il nous faudra évaluer ses capacités à produire des effets liés à la distribution des phases et caractériser leurs conditions d'apparition. Afin d'obtenir ces informations, nous considérerons au chapitre 4 des situations tests principalement axées sur l'importance de certains paramètres tels le contraste inter-phase, la non linéarité et la fraction volumique. Ce chapitre sera également l'occasion de vérifier l'implémentation du modèle en confrontant les résultats obtenus, dans des cas simples, avec certains résultats issus de la littérature ou fournis par des logiciels à notre disposition. Après avoir considéré ces situations de référence nous chercherons à nous rapprocher du matériau d'étude. Pour ce faire, nous proposerons des mesures expérimentales permettant d'obtenir des caractérisations directement utilisables dans le cadre du modèle précédemment introduit. Ces résultats expérimentaux, obtenus en collaboration avec l'université de Sheffield, constitueront des données de référence que rions chercherons à reproduire dans la suite du travail. Le chapitre 6 propose de telles comparaisons modèle/expérience intégrant l'évolution micro structurale qui apparaît au cours de la sollicitation. Dans cette partie, ainsi que dans celle qui suit, nous discuterons des résultats obtenus, des défauts de nos modélisations et de nos caractérisations expérimentales, afin de pouvoir conclure quant à la pertinence de notre approche. L'ensemble de ce travail se place dans le cadre des comportements non linéaires, il sera donc question de linéarisation dans ce mémoire, néanmoins ce n'est pas sur cet aspect que se situent, à proprement parler, les développements nouveaux. En effet, une autre étape critique du traitement d'un polycristal biphasé, qui est d'ailleurs fondamentale pour tous les matériaux hétérogènes, est la représentation de la microstructure ainsi que celle des mécanismes responsables du comportement mécanique des matériaux. La théorie des composites nous offre des outils éprouvés pour mener à bien cette description, nous avons donc essayé ici, de mettre à profit ces connaissances dans un cas où le modèle auto-cohérent semble trop restrictif

Configurable events to enable efficient diagnostics data collection in ISNS based ISCSI network

This disclosure relates to the field of diagnostics data collection in a data network of ISCSI devices capable of reporting diagnostic data like temperature, power etc (hereafter simply referred as data network) and the paper discusses a method of delegating decision of event generation to the reporting device, upon which meaningful diagnostic data is ready to be collected by a data collecting system

Acoustique des bulles cubiques : six oscillateurs couplés

5 pages with 4 figures, supplementary material with two figures. To appear in Physical Review Letters, with Editors' suggestionInternational audienceIn this manuscript we introduce cubic bubbles that are pinned to 3D printed millimetric frames immersed in water. Cubic bubbles are more stable over time and space than standard spherical bubbles, while still allowing large oscillations of their faces. We found that each face can be described as a harmonic oscillator coupled to the other ones. These resonators are coupled by the gas inside the cube but also by acoustic interactions in the liquid. We provide an analytical model and 3D numerical simulations predicting the resonance with a very good agreement. Acoustically, cubic bubbles prove to be good monopole sub-wavelength emitters, with non-emissive secondary surfaces modes

Estimating the parameters of a generalized lambda distribution

International audienceThe method of moments is a popular technique for estimating the parameters of a generalized lambda distribution (GLD), but published results suggest that the percentile method gives superior results. However, the percentile method cannot be implemented in an automatic fashion, and automatic methods, like the starship method, can lead to prohibitive execution time with large sample sizes. A new estimation method is proposed that is automatic (it does not require the use of special tables or graphs), and it reduces the computational time. Based partly on the usual percentile method, this new method also requires choosing which quantile u to use when fitting a GLD to data. The choice for u is studied and it is found that the best choice depends on the final goal of the modeling process. The sampling distribution of the new estimator is studied and compared to the sampling distribution of estimators that have been proposed. Naturally, all estimators are biased and here it is found that the bias becomes negligible with sample sizes n⩾2×103. The .025 and .975 quantiles of the sampling distribution are investigated, and the difference between these quantiles is found to decrease proportionally to View the MathML source. The same results hold for the moment and percentile estimates. Finally, the influence of the sample size is studied when a normal distribution is modeled by a GLD. Both bounded and unbounded GLDs are used and the bounded GLD turns out to be the most accurate. Indeed it is shown that, up to n=106, bounded GLD modeling cannot be rejected by usual goodness-of-fit tests

One channel spatio-temporal inversion of acoustic wave in reverberant cavities

International audienceIt has been recently shown that it was possible to optimally recover the Green functions from a complex wave field despite of a non-isotropic distribution of noise sources. The method used is based on a particular use of the inverse filter (IF) formalism which is called the passive IF. Based on this formalism, we have investigated the possibility to control the spatio-temporal degrees of freedom in a reverberant cavity for the focusing of waves (active processes). The understanding of this phenomenon can be very useful in a lot of different applications like in acoustical imaging, seismology, or telecommunications. In the present work, the spatio-temporal focalization of ultrasounds in reverberant cavities is studied using medical arrays and water tanks. Through experiments, a complete spatio-temporal inversion is realized to synthesize optimized emitting signals. The result generalizes the focalization control over a spatial vector and during an arbitrary time window

Reply to Pallotti et al. comment on “Boitrelle et al. The sixth edition of the who manual for human semen analysis: A critical review and swot analysis. Life 2021, 11, 1368"

We would like to thank F. Pallotti and his colleagues for their positive comments [1] on our SWOT analysis of the strengths, weaknesses, threats and opportunities of the sixth edition of the WHO manual on semen analysis [2]. They have raised two concerns: the re-introduction of the category of rapidly moving sperm, and the dropping of the reference range. With regard to the re-introduction of the distinction between rapidly progressive (type a) motility and sluggish progressive (type b) motility, Pallotti et al. raised the point that this distinction is difficult to make visually and will, therefore, lead to “approximation” and subjective reporting with “reduced standardization”. This is a valid concern and was the reason why the editors of the fifth edition of the WHO manual removed this distinction (which was present in the fourth edition) and created the combined category of “progressive motility”

Impact of antioxidant therapy on natural pregnancy outcomes and semen parameters in infertile men: A systematic review and meta-analysis of randomized controlled trials

Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS.Materials and Methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines.Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair.Conclusions: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful

Carica papaya leaves: One of dynamic plant parts having multiple therapeutic activities

Introduction: Papaya (Carica papaya Linn.) belongs to the Caricaceae family. Papaya is well known around the world for its medicinal and nutritional properties. Various parts of the plant like, fruits, roots, bark, peel, seeds and pulp are known to have medicinal properties and scientifically established for the various properties. Since the ancient times, part of plants has been utilized for their medicinal values. The plant contains high amount of vitamins A, B and C as well as proteolytic enzyme such as papain and chymopapain. Due to such type of versatile phytoconstituents, the plants show lots of pharmacological application. In this review article we summarized the information regarding the various pharmacological activities of papaya leaf such as anticancer, anti-inflammatory, antidiabetic, antispasmodic, antifungal, antisickling, antioxidant, antimicrobial, antimalarial, as well as helps in proper digestion, hair growth, skin related problems and relief in menstrual pain. Methods: All information presented in this review article regarding the beneficial application of Carica papaya leaf extract has been acquired by imminent various electronic databases including Scopus, Google scholar, Science Direct, Web of science, and PubMed. Result: The papaya plant, including fruit, leaves, seed, bark, latex and its ingredients, plays an important part in the management of progressive illness. The papaya leaf contains active ingredients such as alkaloids, glycosides, phenols, tannins, saponins and the flavonoids responsible for the basketful therapeutic function. Conclusion: The main findings showed that papaya leaf extract has strong medicinal properties. The leaves of papaya may also useful in cosmetic applications